Emboli form, for example, as a result of the presence of foreign matter in the bloodstream or can arise spontaneously. Vascular emboli are a major single causative agent for multiple human pathologies, and are a leading cause of disability and death. Clots or thrombi that become dislodged from the point of origin are termed emboli. Such particulate matter may originate from a blood clot occurring in the heart, a foreign body, or may be derived from body tissues. For example, atherosclerosis (fatty or calcified deposits in blood vessel walls), may cause emboli to form. Moreover, clots can form on the luminal surface of the atheroma, as platelets, fibrin, red blood cells and activated clotting factors may adhere to the surface of blood vessels to form a clot. Blood clots or thrombi may also form in the veins of subjects who are immobilized, particularly in the legs of bedridden or other immobilized patients. These clots may then travel in the bloodstream, potentially to the arteries of the lungs, leading to a common, often-deadly disease called ‘pulmonary embolus’. Thrombus formation, and subsequent movement to form an embolus, may occur in the heart or other parts of the arterial system, causing acute reduction of blood supply and hence ischemia. The ischemic damage often leads to tissue necrosis of organs such as the kidneys, retina, bowel, heart, limbs, brain or other organs, or even death.
Cerebral function and viability are dependent on uninterrupted blood flow through the microvasculature for adequate oxygen and glucose delivery (Powers et al., 1985). Thus, robust mechanisms to ensure microvascular patency must have evolved. The fibrinolytic system is a highly regulated mechanism that ensures the degradation of fibrin clots occluding cerebral blood vessels (Collen, 1980) including terminal arterioles and capillaries (Levin and del Zoppo, 1994). However, microvessels, because of their small diameter and relative low flow velocity, may be prone to occlusion by clots as well as detritus not susceptible to fibrinolysis such as fragments of atheromatous plaques (Rapp et al., 2000, herein incorporated by reference in its entirety).